THYMOCYTES EXPRESSING CD8 DIFFERENTIATE INTO CD4+ CELLS FOLLOWING INTRATHYMIC INJECTION

THYMOCYTES EXPRESSING CD8 DIFFERENTIATE INTO CD4+ CELLS FOLLOWING INTRATHYMIC INJECTION
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DOI:
10.1073/pnas.85.22.8633
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发表时间:
1988-11-01
影响因子:
11.1
通讯作者:
BEVAN, MJ
BEVAN, MJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
NIKOLICZUGIC, J;BEVAN, MJ

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根据CD4和CD8分子的细胞表面表达,小鼠胸腺细胞可分为四个群体:包括CD4-、CD8-双阴性和CD4+、CD8+双阳性亚群,这两种亚群主要由未成熟细胞组成,以及单阳性、CD4+和CD8+,分别包含功能性辅助细胞或杀伤细胞。双阴性子集包含其他三个群体的前体,并且可以在静脉内或胸腺内转移到受辐射宿主体内后重建胸腺。为了建立胸腺内发育过程中 CD4 和 CD8 表达的序列,我们通过静脉内或胸腺内过继转移研究了高度纯化的 CD8+ 胸腺细胞的分化潜力。与双阴性胸腺细胞亚群不同,CD8+细胞在静脉转移后不具有归巢至胸腺的能力。然而,当CD8+胸腺细胞直接注射到胸腺中时,它们的数量增加并产生CD4+、CD8+双阳性和CD4+单阳性子代。此外,注射的 CD8+ 前体细胞中 CD4+ 细胞的出现速度比双阴性子集更快。表达高表面密度 CD8 的细胞转化为双阳性和 CD4+ 后代,数量不会增加,而表达低表面密度标记的 CD8+ 细胞则大幅扩增并产生分化的后代。结果表明,CD8 表达是成熟 CD4+ T 细胞分化途径的中间步骤。
Based on the cell surface expression of CD4 and CD8 molecules, murine thymocytes can be divided into four populations: these include CD4-, CD8- double-negative and CD4+, CD8+ double-positive subpopulations, both of which consist largely of immature cells, and the single positive, CD4+ ro CD8+, subsets that contain functional helper or killer cells, respectively. The double-negative subset contains precursors of the other three populations and can reconstitute the thymus following intravenous or intrathymic transfer into irradiated hosts. In an attempt to establish the sequence of CD4 and CD8 expression during intrathymic development, we investigated the differentiation potential of highly purified CD8+ thymocytes by using intravenous or intrathymic adoptive transfer. Unlike the double-negative thymocyte subset, CD8+ cells do not have the ability to home to the thymus following intravenous transfer. However, when CD8+ thymocytes were injected directly into the thymus, they increased in number and gave rise to CD4+, CD8+ double-positive and CD4+ single-positive progeny. Furthermore, the rate of appearance of CD4+ cells from injected CD8+ precursors was faster than from the double-negative subset. Cells expresssing a high surface density of CD8 convert to double-positive and CD4+ progeny without increasing in number, whereas CD8+ cells expressing a low surface density of the marker expand greatly and give rise to differentiated progeny. The results suggest that CD8 expression is an intermediate step on the differentiation pathway of mature CD4+ T cells.